Respiratory: Basics

• Anatomy: The Airways | Lungs, Lobes and Segments | Pleura and Surface Anatomy | Muscles of Breathing | Blood Supply of the Lungs | Cells of the Airways and Alveoli | Lung Development
• Physiology: Mechanics of Breathing | Lung Volumes | Ventilation and Dead Space | Gas Exchange | Ventilation–Perfusion Matching | Causes of Hypoxaemia | Oxygen Transport | Carbon Dioxide Transport | Control of Breathing | Acid–Base Balance | Lung Defences | Exercise, Altitude, Pregnancy and Sleep | Normal Values
• Pharmacology: Inhaler Devices and Technique | Bronchodilators | Inhaled Corticosteroids | Combination Inhalers, AIR and MART | Montelukast and Theophylline | Oral and IV Steroids and Magnesium | Biologics for Severe Asthma | Mucolytics and CF Modulators | Antifibrotic Drugs | Oxygen as a Drug | Antibiotics and TB Drugs | Pulmonary Hypertension Drugs | Drugs That Affect Breathing | Drugs That Damage the Lungs
• Revision: Drug Reference Table | Spot the Answer | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🫁 Respiratory anatomy, physiology and pharmacology — the lungs have one job: to get oxygen into the blood and carbon dioxide out. Understanding the airways, the mechanics of breathing, ventilation–perfusion matching and the oxygen dissociation curve explains most respiratory symptoms, blood gases and treatments. Most respiratory drugs either open the airways, reduce airway inflammation, clear mucus, slow fibrosis or treat infection.
Your four questions for every drug: How does it work? What is it used for? What are the important side effects and safety issues? What does it interact with, and how is it monitored?

The Airways

• Upper airway — nose (warms, humidifies and filters air), pharynx, larynx (vocal cords — the narrowest point in adults; in young children the narrowest point is below the cords, at the cricoid).
• Trachea — about 10–12 cm long, from C6 to the carina at about T4/T5 (level of the sternal angle); C-shaped cartilage rings, open at the back.
• Main bronchi:
  • Right main bronchus — wider, shorter and more vertical — inhaled foreign bodies and aspiration go to the right lung more often (lower lobe when upright; posterior segment of the upper lobe and apical segment of the lower lobe when lying down).
  • Left main bronchus — longer, more horizontal, passes under the aortic arch.
• Branching — about 23 generations: lobar → segmental bronchi → bronchioles → terminal bronchioles (end of the conducting zone — no gas exchange) → respiratory bronchioles → alveolar ducts → alveoli (the respiratory zone; about 300–500 million alveoli, surface area about 70 m²).
• Cartilage is present down to the small bronchi; bronchioles have no cartilage and rely on smooth muscle and surrounding lung tissue to stay open (they collapse in emphysema — air trapping).
• Airway smooth muscle — contracts in asthma (bronchospasm); controlled by the vagus (muscarinic M3 receptors — constrict) and circulating adrenaline (beta-2 receptors — relax).

Lungs, Lobes and Segments

• Right lung — three lobes (upper, middle, lower), divided by the oblique and horizontal fissures; 10 bronchopulmonary segments.
• Left lung — two lobes (upper and lower), one oblique fissure; the lingula (part of the upper lobe) is the equivalent of the right middle lobe; the cardiac notch makes room for the heart.
• Bronchopulmonary segments — each has its own bronchus and artery, so a segment can be removed surgically.
• Hilum — where the main bronchus, pulmonary artery, pulmonary veins, bronchial vessels, lymph nodes and nerves enter the lung (enlarged hilar nodes — sarcoidosis, TB, lymphoma, lung cancer).
• Lobes on examination and X-ray:
  • From the front, you mainly hear the upper lobes (and right middle lobe on the right).
  • From the back, you mainly hear the lower lobes.
  • Right middle lobe pneumonia blurs the right heart border; lingula blurs the left heart border; lower lobe disease blurs the diaphragm (the "silhouette sign").
• Lymphatics drain to hilar and mediastinal nodes (important in lung cancer staging).

Pleura and Surface Anatomy

• Pleura — two layers with a thin film of fluid between them (the pleural space, normally about 10–20 mL):
  • Visceral pleura — covers the lung; no pain fibres.
  • Parietal pleura — lines the chest wall, diaphragm and mediastinum; pain-sensitive (intercostal nerves — localised pleuritic pain; the central diaphragm via the phrenic nerve — pain referred to the shoulder tip).
  • The pleural space has negative pressure, which keeps the lung expanded; air (pneumothorax) or fluid (effusion) lets the lung collapse.
• Surface markings ("6, 8, 10" for the lungs; pleura about two ribs lower):
  • Lung lower edge — 6th rib in the mid-clavicular line, 8th in the mid-axillary line, 10th at the back.
  • Pleura lower edge — 8th, 10th and 12th ribs (the gap is the costodiaphragmatic recess where effusions collect).
  • Lung apex — about 2–3 cm above the medial third of the clavicle (at risk with subclavian lines — pneumothorax).
  • Oblique fissure — from about T3 at the back to the 6th costal cartilage at the front; horizontal fissure (right) — along the 4th costal cartilage.
• Intercostal neurovascular bundle — runs in the groove under each rib (vein, artery, nerve — "VAN" from top to bottom) — so needles and drains are inserted just above the rib below.
• Safe triangle for chest drains — lateral border of pectoralis major, lateral border of latissimus dorsi, a line at the level of the nipple (5th intercostal space), and the base of the axilla.

Muscles of Breathing

• Diaphragm — the main muscle of breathing (about 70% of quiet inspiration); dome-shaped; contracts and flattens to enlarge the chest.
  • Supplied by the phrenic nerves (C3, C4, C5 — "C3, 4, 5 keeps the diaphragm alive") — high cervical spinal cord injury stops breathing.
  • Openings — IVC at T8, oesophagus at T10, aorta at T12.
  • Diaphragm weakness — orthopnoea, breathlessness lying flat or in water, paradoxical inward movement of the abdomen on breathing in, FVC falls on lying down.
• External intercostals — lift the ribs ("bucket handle" and "pump handle" movements).
• Accessory muscles of inspiration — sternocleidomastoid, scalenes, trapezius — used in respiratory distress (a sign of increased work of breathing).
• Expiration — normally passive (elastic recoil of the lungs); active in exercise, coughing and airway obstruction (internal intercostals, abdominal muscles).
• Upper airway muscles (genioglossus) keep the throat open — they relax in sleep, alcohol and sedation (obstructive sleep apnoea).

Blood Supply of the Lungs

• Two blood supplies:
  • Pulmonary circulation — the whole cardiac output passes through the lungs from the right ventricle; low pressure (mean about 15 mmHg) and low resistance; returns oxygenated blood to the left atrium via the pulmonary veins.
  • Bronchial circulation — small systemic arteries from the aorta supply the airways and lung tissue; source of massive haemoptysis (treated by bronchial artery embolisation).
• Because of the dual supply, pulmonary infarction is uncommon after PE (usually with small peripheral clots — pleuritic pain and haemoptysis).
• Hypoxic pulmonary vasoconstriction — small pulmonary arteries constrict in areas with low oxygen, diverting blood to better-ventilated lung (the opposite of systemic arteries). Widespread chronic hypoxia (COPD, altitude, sleep apnoea) causes pulmonary hypertension and right heart failure (cor pulmonale).
• Recruitment and distension — the pulmonary circulation opens more vessels as cardiac output rises (e.g. in exercise), so pressure barely rises.
• Lymphatics clear fluid from the interstitium — fluid leaks into the alveoli when capillary pressure is high (heart failure) or capillaries are damaged (ARDS).

Cells of the Airways and Alveoli

• Ciliated columnar epithelium — lines the airways down to the bronchioles; cilia beat mucus upwards (the mucociliary escalator); damaged by smoking; abnormal in primary ciliary dyskinesia.
• Goblet cells and submucosal glands — produce mucus (increased in chronic bronchitis and asthma).
• Club cells (Clara cells) — in the bronchioles; secrete protective proteins.
• Type I pneumocytes — flat cells forming about 95% of the alveolar surface; very thin barrier for gas exchange; easily damaged.
• Type II pneumocytes — make surfactant and can divide to repair the alveoli.
• Surfactant — lowers surface tension so small alveoli don't collapse at the end of breathing out (Laplace's law); deficient in premature babies (respiratory distress syndrome) and damaged in ARDS.
• Alveolar macrophages — engulf dust and microbes ("dust cells").
• Mast cells and eosinophils — key in allergic (type 2) asthma; release histamine, leukotrienes and other mediators.
• Neuroendocrine (Kulchitsky) cells — origin of carcinoid tumours and small cell lung cancer.

Lung Development

• The lungs develop from a bud of the foregut (so a tracheo-oesophageal fistula can occur with oesophageal atresia).
• Airways branch through the first two trimesters; gas-exchanging sacs form from about 24 weeks; alveoli keep multiplying until about age 8.
• Surfactant production starts around 24 weeks and is usually enough by about 34–36 weeks.
• Antenatal corticosteroids (dexamethasone or betamethasone) speed lung maturation — offered for threatened preterm birth (from 24 weeks to 33+6 weeks, and considered up to 35+6 weeks).
• Congenital diaphragmatic hernia — abdominal organs in the chest compress the developing lung (pulmonary hypoplasia).
• Oligohydramnios (e.g. kidney agenesis, ruptured membranes) also causes pulmonary hypoplasia — the fetus needs to "breathe" amniotic fluid for lungs to grow.

Mechanics of Breathing

• Inspiration — the diaphragm and intercostals enlarge the chest → pleural pressure becomes more negative → alveolar pressure falls below atmospheric pressure → air flows in.
• Expiration — elastic recoil of the lungs pushes air out (passive at rest).
• Compliance — how easily the lungs stretch (change in volume per change in pressure):
  • Low compliance (stiff lungs) — pulmonary fibrosis, oedema, ARDS, pneumonia; also chest wall problems (obesity, kyphoscoliosis) — restrictive pattern; small, fast breaths.
  • High compliance (floppy lungs) — emphysema (loss of elastic tissue) — lungs over-inflate and air is trapped.
• Airway resistance:
  • Mostly in the medium-sized bronchi (not the small airways, because there are so many of them in parallel).
  • Resistance rises sharply as airways narrow — by Poiseuille's law, resistance is proportional to 1/radius⁴ (halving the radius increases resistance 16 times).
  • Increased by bronchospasm, mucus, oedema, and loss of airway support (emphysema) — obstructive pattern.
• Dynamic airway compression — on forced expiration, pressure around the airways rises and squeezes them shut (worse in emphysema — hence pursed-lip breathing, which keeps airways open).
• Work of breathing — rises with stiff lungs or narrow airways; signs include tachypnoea, accessory muscle use, recession and tripod positioning; exhaustion leads to type 2 respiratory failure.
• Laminar and turbulent flow — turbulent flow in large airways and at narrowings produces sounds (stridor, wheeze); heliox (helium–oxygen, low density) reduces turbulent resistance in upper airway obstruction.

Lung Volumes

• Obstruction (COPD, asthma) — air trapping: raised RV, FRC and TLC (hyperinflation).
• Restriction (fibrosis, obesity, chest wall, neuromuscular) — reduced TLC, VC and FRC.
• FRC falls when lying flat, in obesity, pregnancy and anaesthesia — so oxygen stores fall and hypoxia comes on faster (pre-oxygenate before intubation).
• Spirometry measures FEV1 and FVC; RV, FRC and TLC need body plethysmography or gas dilution (see the Respiratory Investigations chapter).

Ventilation and Dead Space

• Minute ventilation = tidal volume × respiratory rate (about 500 mL × 12 = 6 L/min).
• Anatomical dead space — the conducting airways (no gas exchange) — about 150 mL (roughly 2 mL/kg).
• Alveolar ventilation = (tidal volume − dead space) × rate — this is what removes CO2.
• Fast, shallow breathing is inefficient — e.g. 25 breaths of 200 mL = 5 L/min minute ventilation, but only (200 − 150) × 25 = 1.25 L/min alveolar ventilation → CO2 rises (seen in exhaustion, neuromuscular weakness, opioid toxicity).
• Physiological dead space = anatomical plus alveolar dead space (alveoli that are ventilated but not perfused — e.g. PE, emphysema, low cardiac output).
• PaCO2 is inversely proportional to alveolar ventilation — halve the ventilation, double the CO2. So a high PaCO2 always means inadequate alveolar ventilation (type 2 respiratory failure).
• Regional differences — in an upright person, the lung bases receive more ventilation and more blood flow than the apices (gravity); TB favours the apices (high oxygen, less blood flow).

Gas Exchange

• Diffusion across the alveolar–capillary membrane follows Fick's law — faster with a larger surface area, a bigger pressure difference, and a thinner membrane:
  • Less surface area — emphysema, lung resection, PE (less perfused capillary bed).
  • Thicker membrane — fibrosis, oedema.
  • Measured by gas transfer (TLCO/DLCO) using carbon monoxide.
• CO2 diffuses about 20 times more easily than oxygen — so diffusion problems cause hypoxaemia (especially on exercise) long before CO2 rises.
• Blood normally spends about 0.75 seconds in the capillary but equilibrates in about 0.25 seconds — there's reserve, used up in exercise (desaturation on walking in ILD).
• Alveolar gas equation — estimates the oxygen in the alveoli:
  • PAO2 = FiO2 × (atmospheric pressure − water vapour pressure) − PaCO2 ÷ 0.8.
  • On room air at sea level: PAO2 ≈ 20 − (PaCO2 × 1.25) kPa (about 13.7 kPa if PaCO2 is 5 kPa).
• A–a gradient = PAO2 − PaO2 — normally under about 2 kPa in young adults (rises with age):
  • Normal gradient with low PaO2 — hypoventilation (lungs healthy — e.g. opioids, neuromuscular weakness) or low inspired oxygen (altitude).
  • Raised gradient — a lung problem: V/Q mismatch, shunt or diffusion impairment.

Ventilation–Perfusion Matching

• For efficient gas exchange, ventilation (V) and blood flow (Q) must match — the overall V/Q ratio is about 0.8.
• Low V/Q (perfused but poorly ventilated) — asthma, COPD, pneumonia, atelectasis — the commonest cause of hypoxaemia; corrects with extra oxygen.
• Shunt (V/Q = 0 — perfused but not ventilated at all) — collapsed or fluid-filled alveoli (pneumonia, ARDS, oedema), intracardiac shunts, pulmonary AVMs — hypoxaemia that responds poorly to oxygen; needs PEEP or CPAP to open alveoli.
• Dead space (V/Q = infinity — ventilated but not perfused) — PE, emphysema, low cardiac output; raises the work of breathing.
• Hypoxic pulmonary vasoconstriction limits V/Q mismatch by diverting blood away from poorly ventilated areas.
• Why some drugs worsen oxygenation — bronchodilators and vasodilators can release hypoxic vasoconstriction, briefly worsening V/Q and saturations.
• Why high-flow oxygen raises CO2 in COPD — mainly by releasing hypoxic vasoconstriction (more blood to poorly ventilated areas → more dead space) and the Haldane effect (oxygenated haemoglobin carries less CO2) — not mainly by abolishing "hypoxic drive".
• Positioning — in one-sided lung disease, lying with the good lung down improves oxygenation (more blood flow to the better lung).

Causes of Hypoxaemia

• Type 1 respiratory failure — PaO2 under 8 kPa with normal or low PaCO2 (V/Q mismatch, shunt, diffusion).
• Type 2 respiratory failure — PaO2 under 8 kPa with PaCO2 over 6.0 kPa (hypoventilation — COPD, neuromuscular, sedation, exhaustion).
• Tissue hypoxia without hypoxaemia — anaemia, carbon monoxide poisoning, low cardiac output, cyanide (cells can't use oxygen).

Oxygen Transport

• Most oxygen (about 98%) is carried bound to haemoglobin; only a little is dissolved in plasma. Each gram of haemoglobin carries about 1.34 mL of oxygen when fully saturated.
• Oxygen content ≈ 1.34 × Hb (g/L ÷ 10) × saturation — so anaemia reduces oxygen delivery even with normal saturations.
• Oxygen dissociation curve — S-shaped (haemoglobin binds oxygen more easily as more is bound — cooperative binding):
  • The flat upper part — saturation stays high even if PaO2 falls a bit (safety margin); also why giving more oxygen to someone at 97% adds little.
  • The steep part (below about 8 kPa / 90%) — small falls in PaO2 cause big falls in saturation; tissues can unload oxygen easily.
  • P50 (PaO2 at 50% saturation) — about 3.5 kPa.
  • Rough guide — PaO2 8 kPa ≈ 90%; PaO2 5.3 kPa ≈ 75% (mixed venous blood).
• Right shift (oxygen released more easily to tissues) — raised CO2, acidosis (Bohr effect), raised temperature, raised 2,3-DPG (anaemia, altitude, chronic hypoxia), exercise.
• Left shift (haemoglobin holds on to oxygen) — fetal haemoglobin (helps the fetus take oxygen from the mother), carbon monoxide, alkalosis, low temperature, low 2,3-DPG (stored blood), methaemoglobin.
• Carbon monoxide — binds haemoglobin about 240 times more strongly than oxygen and shifts the curve left — pulse oximetry reads falsely normal; measure carboxyhaemoglobin on a blood gas; give 100% oxygen (shortens CO half-life from about 5 hours to about 1 hour).
• Methaemoglobinaemia (dapsone, local anaesthetics like prilocaine and benzocaine, nitrites) — iron oxidised so it can't carry oxygen; chocolate-brown blood, oximetry about 85% regardless; treat with methylene blue.
• Cyanosis — visible when there is about 50 g/L of deoxygenated haemoglobin — may be absent in anaemia, and seen earlier in polycythaemia.

Carbon Dioxide Transport

• CO2 is carried in three forms:
  • Bicarbonate (about 70%) — CO2 + water → carbonic acid → H+ + HCO3− (fast in red cells via carbonic anhydrase); bicarbonate moves out of the cell in exchange for chloride (the "chloride shift").
  • Bound to haemoglobin as carbamino compounds (about 20–25%).
  • Dissolved in plasma (about 5–10%).
• Haldane effect — deoxygenated haemoglobin carries more CO2; when blood is oxygenated in the lungs, CO2 is released. Giving high-flow oxygen to someone with COPD releases CO2 from haemoglobin, adding to hypercapnia.
• CO2 and pH — rising CO2 makes blood more acidic (respiratory acidosis); the kidneys compensate over days by keeping bicarbonate.
• CO2 is a vasodilator in the brain — high CO2 causes headache, bounding pulse, warm hands, flapping tremor, drowsiness and raised intracranial pressure; low CO2 (hyperventilation) causes cerebral vasoconstriction, dizziness and tingling (and is used briefly to lower intracranial pressure).
• Acetazolamide (carbonic anhydrase inhibitor) — causes a mild metabolic acidosis that stimulates breathing (used for altitude sickness).

Control of Breathing

• Respiratory centres in the medulla and pons set the rhythm; the cortex allows voluntary control (breath-holding, speech).
• Central chemoreceptors (medulla) — respond to CO2 via changes in pH of the cerebrospinal fluid — the main minute-to-minute drive to breathe.
• Peripheral chemoreceptors (carotid bodies — glossopharyngeal nerve; aortic bodies — vagus) — respond mainly to low oxygen (especially PaO2 under about 8 kPa), and also to acidosis and CO2.
• Chronic hypercapnia (some COPD patients) — the central response to CO2 is blunted as bicarbonate rises, so low oxygen becomes relatively more important — but the main reason oxygen raises CO2 is V/Q change and the Haldane effect (see above).
• Lung receptors — stretch receptors (Hering–Breuer reflex), irritant receptors (cough, bronchoconstriction), J receptors (stimulated by oedema and fibrosis — breathlessness and fast breathing).
• Things that reduce the drive to breathe — opioids, benzodiazepines, alcohol, anaesthetics, gabapentinoids, brainstem stroke, hypothyroidism, sleep.
• Things that increase it — metabolic acidosis (Kussmaul breathing in DKA), hypoxia, fever, anxiety, pain, PE, salicylates, progesterone (pregnancy), stimulants.
• Breathing patterns:
  • Cheyne–Stokes — waxing and waning breathing with pauses — heart failure, stroke, opioids, altitude.
  • Kussmaul — deep, sighing breaths — metabolic acidosis.
  • Apneustic and ataxic breathing — brainstem damage.

Acid–Base Balance

• Henderson–Hasselbalch — pH depends on the ratio of bicarbonate (kidneys) to CO2 (lungs). The lungs adjust CO2 in minutes; the kidneys adjust bicarbonate over 2–5 days.
• Four primary disturbances:
  • Respiratory acidosis — high CO2 (hypoventilation — COPD, opioids, neuromuscular). Acute — low pH, normal bicarbonate; chronic — near-normal pH, high bicarbonate (renal compensation).
  • Respiratory alkalosis — low CO2 (hyperventilation — anxiety, PE, pneumonia, pain, early salicylate poisoning, pregnancy, altitude).
  • Metabolic acidosis — low bicarbonate (DKA, lactic acidosis, AKI, diarrhoea); the lungs compensate by blowing off CO2 (Kussmaul breathing); check the anion gap.
  • Metabolic alkalosis — high bicarbonate (vomiting, diuretics); the lungs compensate by breathing less (CO2 rises — limited by hypoxia).
• Acute-on-chronic respiratory acidosis (COPD exacerbation) — high bicarbonate (chronic) but pH under 7.35 (acute rise in CO2) — consider NIV if pH is under 7.35 and PaCO2 over 6.5 kPa despite optimal treatment.
• Compensation never overcorrects — if the pH is on the "wrong side", there's a second primary disturbance.
• Step-by-step blood gas interpretation is covered in the Respiratory Investigations and Respiratory Emergencies chapters.

Lung Defences

• Nose and upper airway — filtering and humidification; large particles trapped.
• Cough and sneeze reflexes — impaired by stroke, sedation, neuromuscular disease, rib fractures, pain — leading to aspiration pneumonia.
• Mucociliary escalator — damaged by smoking, viral infections, dehydration; abnormal in cystic fibrosis (thick mucus from CFTR defect) and primary ciliary dyskinesia (bronchiectasis, sinusitis, infertility, situs inversus in Kartagener syndrome).
• Immune defences — secretory IgA, alveolar macrophages, neutrophils, surfactant proteins, lymphocytes.
  • Antibody deficiency — recurrent bacterial chest infections and bronchiectasis.
  • T-cell deficiency (HIV, steroids, transplant drugs) — PCP, TB, fungal and viral infections.
  • Neutropenia — bacterial and fungal (Aspergillus) infections.
• Alpha-1 antitrypsin — made in the liver; protects lung tissue from neutrophil elastase; deficiency causes early emphysema (lower lobes) and liver disease.

Exercise, Altitude, Pregnancy and Sleep

• Exercise — minute ventilation can rise more than tenfold; in healthy people, the heart (not the lungs) usually limits exercise; lung disease limits it through breathlessness, desaturation and hyperinflation.
• Altitude — the oxygen fraction stays at 21%, but barometric pressure falls, so inspired oxygen falls:
  • Hypoxia → hyperventilation → respiratory alkalosis → kidneys excrete bicarbonate over days (acclimatisation); more 2,3-DPG; polycythaemia over weeks.
  • Hypoxic pulmonary vasoconstriction → pulmonary hypertension → risk of high-altitude pulmonary oedema.
  • Aircraft cabins are pressurised to the equivalent of about 1,500–2,400 m (PaO2 falls to about 8 kPa in healthy people) — see the fitness-to-fly guidance.
• Pregnancy — progesterone increases breathing (tidal volume up) → mild respiratory alkalosis (PaCO2 about 4 kPa) with compensated low bicarbonate; FRC falls as the uterus pushes up the diaphragm; breathlessness is common; a "normal" PaCO2 of 5.5 kPa in late pregnancy may mean the mother is tiring (e.g. severe asthma).
• Sleep — less drive to breathe, relaxed upper airway muscles, less response to CO2 — worsens sleep apnoea, hypoventilation in obesity, neuromuscular disease and COPD (REM sleep is the most vulnerable time).
• Ageing — loss of elastic recoil, stiffer chest wall, weaker muscles, a wider A–a gradient, and lower PaO2 (about 0.5 kPa less per decade after middle age is common).
• Diving — pressure rises 1 atmosphere for every 10 m; risks include barotrauma, pneumothorax, decompression illness, and air embolism.

Normal Values

Inhaler Devices and Technique

• Why inhalers — deliver drug straight to the airways: fast action, lower doses, fewer systemic side effects. Poor technique is the commonest reason inhalers "don't work" — check it at every review.
• Pressurised metered-dose inhaler (pMDI) — "puffer"; needs coordination of pressing and breathing in slowly and deeply, then holding the breath for about 10 seconds.
  • Use with a spacer — improves lung delivery and reduces mouth deposition (oral thrush); essential for children and in acute attacks (as effective as nebulisers in most).
  • Spacers — wash monthly, air-dry; replace every 6–12 months.
• Dry powder inhaler (DPI) (e.g. Turbohaler, Accuhaler, Ellipta) — breath-activated; needs a quick, forceful breath in; less suitable in severe attacks, young children and frail people with weak breaths.
• Soft mist inhaler (Respimat) — slow-moving mist; less coordination needed.
• Nebulisers — for severe attacks and people who can't use inhalers; driven by oxygen in asthma, but by air in COPD with hypercapnia (with supplemental nasal oxygen as needed).
• Environmental impact — pMDIs contain propellant gases with a high carbon footprint; DPIs or soft mist inhalers are lower-carbon alternatives where clinically suitable.
• Counting doses — patients should know when their inhaler is running out (dose counters).

Bronchodilators

• Beta-2 agonists — stimulate beta-2 receptors on airway smooth muscle → raise cAMP → relaxation.
  • SABA (short-acting) — salbutamol, terbutaline: work in minutes, last 4–6 hours; reliever.
  • LABA (long-acting) — salmeterol (slow onset, 12 hours), formoterol (fast onset, 12 hours — allows use as a reliever in MART/AIR), vilanterol, olodaterol, indacaterol (24 hours).
  • Side effects — tremor, tachycardia and palpitations, hypokalaemia (high doses), lactic acidosis (high-dose nebulised or IV salbutamol), headache, muscle cramps.
  • LABA alone must never be used in asthma — always with an inhaled steroid (increased risk of severe attacks and death).
• Antimuscarinics — block muscarinic (M3) receptors → less vagal bronchoconstriction and mucus secretion.
  • SAMA — ipratropium (in acute asthma and COPD exacerbations).
  • LAMA — tiotropium, umeclidinium, glycopyrronium, aclidinium — once or twice daily; mainly COPD; also add-on in severe asthma.
  • Side effects — dry mouth, constipation, urinary retention (prostate enlargement), blurred vision, and acute angle-closure glaucoma (nebulised drug escaping a face mask into the eyes — use a mouthpiece or goggles).
  • Don't use a LAMA and ipratropium together regularly.
• Theophylline — see Montelukast and Theophylline.

Inhaled Corticosteroids

• Mechanism — switch off inflammatory genes in airway cells → less eosinophilic (type 2) inflammation, less airway hyper-responsiveness; prevent attacks and reduce death in asthma.
• Examples — beclometasone, budesonide, fluticasone (propionate and furoate), mometasone, ciclesonide. Doses are graded as low, moderate or high (devices aren't interchangeable dose-for-dose — prescribe by brand).
• Uses — the foundation of asthma treatment (all adults now use ICS-containing treatment — no SABA-only treatment); COPD with asthmatic features or frequent exacerbations with raised blood eosinophils.
• Local side effects — oral thrush, hoarse voice (dysphonia) — reduce by using a spacer and rinsing the mouth after use.
• Systemic side effects (mainly at high doses) — adrenal suppression (steroid emergency card for high doses), osteoporosis, cataracts and glaucoma, skin thinning and bruising, growth slowing in children (small), raised glucose.
• Pneumonia — increased risk with ICS in COPD (especially fluticasone).
• Step down — once asthma is well controlled for 3 months, reduce to the lowest effective dose.

Combination Inhalers, AIR and MART

• ICS + LABA — budesonide–formoterol, beclometasone–formoterol, fluticasone–salmeterol, fluticasone furoate–vilanterol.
• Asthma (BTS/NICE/SIGN 2024) in adults and young people aged 12 and over:
  • AIR (anti-inflammatory reliever) — as-needed low-dose ICS–formoterol for mild asthma, instead of a SABA alone.
  • MART (maintenance and reliever therapy) — the same ICS–formoterol inhaler taken regularly and also as the reliever; escalate to moderate-dose MART if not controlled.
  • Then — check FeNO and eosinophils, add a LTRA or LAMA, refer for specialist care.
  • Formoterol is used because its onset is fast; salmeterol combinations can't be used as relievers.
  • Maximum daily doses of ICS–formoterol must be explained (e.g. no more than 12 puffs a day of budesonide–formoterol 200/6 in most adults — check the product).
• LABA + LAMA (e.g. umeclidinium–vilanterol, tiotropium–olodaterol) — first-line regular treatment for most people with COPD who remain breathless (NICE NG115).
• Triple therapy (LABA + LAMA + ICS in one inhaler — e.g. fluticasone furoate–umeclidinium–vilanterol, beclometasone–formoterol–glycopyrronium) — COPD with continued exacerbations (especially with raised eosinophils or asthmatic features); severe asthma.
• Fewer devices are better — use one inhaler type where possible to avoid technique confusion.

Montelukast and Theophylline

• Montelukast (leukotriene receptor antagonist):
  • Blocks cysteinyl leukotriene receptors → less bronchoconstriction and inflammation.
  • Uses — add-on in asthma, exercise-induced and aspirin-exacerbated asthma, allergic rhinitis with asthma, preschool wheeze (trial).
  • MHRA warning — neuropsychiatric reactions: sleep disturbance, nightmares, agitation, depression, behaviour changes and suicidal thoughts (children and adults) — warn patients and families and stop if they occur.
  • Rarely associated with eosinophilic granulomatosis with polyangiitis (often unmasked as steroids are reduced).
• Theophylline and aminophylline (methylxanthines):
  • Phosphodiesterase inhibition and adenosine receptor blockade → bronchodilatation; now rarely used.
  • Narrow therapeutic range — plasma level about 10–20 mg/L (55–110 micromol/L); check 4–6 hours after an oral dose, and before and during IV aminophylline.
  • Metabolised by CYP1A2 — levels raised by ciprofloxacin, clarithromycin, erythromycin, fluvoxamine, cimetidine, heart failure, liver disease, viral infection, stopping smoking; lowered by smoking, rifampicin, carbamazepine, phenytoin, alcohol.
  • Toxicity — nausea and vomiting, tachycardia, arrhythmias, seizures, hypokalaemia, hyperglycaemia, agitation — TOXBASE; activated charcoal (repeat doses), correct potassium, treat seizures.
  • Don't give an IV loading dose of aminophylline to someone already taking oral theophylline.

Oral and IV Steroids and Magnesium

• Acute asthma — prednisolone 40–50 mg once daily for at least 5 days (IV hydrocortisone if unable to swallow); no need to taper short courses.
• COPD exacerbation — prednisolone 30 mg daily for 5 days (NICE NG115).
• Other uses — sarcoidosis, organising pneumonia, hypersensitivity pneumonitis, some ILDs, ABPA, eosinophilic lung diseases, airway swelling.
• Side effects of repeated or long courses — hyperglycaemia (check glucose), hypertension, mood disturbance and insomnia, infection, osteoporosis (bone protection for 3 months or more), adrenal suppression (steroid card; don't stop suddenly after 3 weeks or more), weight gain, cataracts, peptic ulcers. Two or more courses a year in asthma means poor control — review and refer.
• Magnesium sulfate — smooth muscle relaxant; IV 1.2–2 g over 20 minutes in acute severe or life-threatening asthma not responding to initial treatment (single dose); also used in some COPD exacerbations. Watch for hypotension and flushing.

Biologics for Severe Asthma